Biology subjects

Simko, J.

Publications and source records attributed to Simko, J..

4 recordsLinked to original sources

bioRxiv2025

Local thalamic interneurons drive spindle termination and enable sleep-dependent learning

The thalamus is central to fundamental brain functions including sensation, attention, and sleep through the precise generation and regulation of neuronal ensemble oscillatory activity. Sensory thalamic circuits are considered feedforward structures, lacking lateral connectivity, while recurrence in the network is mediated by interactions with inhibitory neurons of the thalamic reticular nucleus. Here, we define previously uncharacterized functional roles of local thalamic interneurons, a component of the sensory thalamus whose function has remained unexplored. We demonstrate that local interneuron activation induces rebound oscillations in thalamocortical relay neurons ex vivo and neocortical spindles in vivo, while their inhibition increases spindle occurrence, overall spindle duration and impairs sensory learning. Our findings reveal that local thalamic interneurons have shared and complementary functions to those of thalamic reticular neurons and are required for proper spindle formation and sleep-dependent learning. Together, this work establishes an important neural substrate of thalamocortical circuit function.

neuroscience↗

bioRxiv2024

Modeling speech adaptation to altered sensory feedback through continuous learning of internal sensory predictions

The paper presents a version of an optimization-based model of speech production that reproduces key acoustic and articulatory features of motorsensory adaptation to altered sensory feedback. In the presented approach, the mechanism of motorsensory adaptation is based on regular updates, based on the sensory feedback perceived by the speaker, of two of the speakers internal models used for computing (near)-optimal articulation. These internal models, modeled as separate Artificial Neural Networks, are 1) a model that predicts the acoustic consequences of motor (articulatory commands) and 2) a model that predicts the somatosensory sensations from given motor commands. The paper presents simulations of adaptation experiments that successfully reproduce key acoustic and articulatory features of motorsensory adaptation of speech to altered sensory feedback. These include gradual and incomplete motorsensory adaptation when the auditory (or the somatosensory) feedback is suddenly altered (F1-shifted for the altered auditory feedback, forced jaw movement for altered somatosensory feedback). The presented simulations also show that the rate and magnitude of adaptation behavior depend on a small number of parameters. Variation in the values of these parameters can potentially explain inter-speaker differences in terms of adaptation behavior, including sensory preference.

neuroscience↗

bioRxiv2023

Behavioral control through the direct, focal silencing of neuronal activity

Voltage-gated sodium channel (NaV) activity underlies electrical signaling, synaptic release, circuit function, and, ultimately, behavior. Molecular tools that enable precise control of NaV subpopulations make possible temporal regulation of neuronal activity and cellular communication. To rapidly modulate NaV currents, we have rendered a potent NaV inhibitor, saxitoxin, transiently inert through chemical protection with a novel nitrobenzyl-derived photocleavable group. Light-induced uncaging of the photocaged toxin, STX-bpc, effects rapid inhibitor release and focal NaV block. We demonstrate the efficacy of this reagent for manipulating action potentials in mammalian neurons and brain slice and for altering locomotor behavior in larval zebrafish. Photo-uncaging of STX-bpc is a non-invasive, effective method for reversible, spatiotemporally precise tuning of NaV currents, application of which requires no genetic manipulation of the biological sample.

neuroscience↗

bioRxiv2022

Reconstruction and simulation of thalamoreticular microcircuitry

Thalamoreticular circuitry is known to play a key role in attention, cognition and the generation of sleep spindles, and is implicated in numerous brain disorders, but the cellular and synaptic mechanisms remain intractable. Therefore, we developed the first detailed computational model of mouse thalamus and thalamic reticular nucleus microcircuitry that captures morphological and biophysical properties of [~]14,000 neurons connected via [~]6M synapses, and recreates biological synaptic and gap junction connectivity. Simulations recapitulate multiple independent network-level experimental findings across different brain states, providing a novel unifying cellular and synaptic account of spontaneous and evoked activity in both wakefulness and sleep. Furthermore, we found that: 1.) inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness, in addition to its role in spindle generation; 2.) thalamic interactions generate the characteristic waxing and waning of spindle oscillations; and 3.) changes in thalamic excitability (e.g. due to neuromodulation) control spindle frequency and occurrence. The model is openly available and provides a new tool to interpret spindle oscillations and test hypotheses of thalamoreticular circuit function and dysfunction across different network states in health and disease.

neuroscience↗